The physiological turnover of articular cartilage represents a fine balance between synthesis and degradation. It is a feature of normal growth and development and maintenance of cartilage in the adult. Net cartilage loss is a feature of rheumatoid arthritis and osteoarthritis. It is strongly associated with disability and a low quality of life. Cartilage destruction in rheumatoid arthritis and osteoarthritis is currently diagnosed based on combined clinical symptoms and radiological findings. Damage to articular cartilage occurs early in the disease, long before it can be detected radiologically; damage is detected radiologically only after there is extensive and probably irreversible cartilage loss. Therefore, it is of critical importance that clinicians have biochemical markers for early diagnosis of cartilage damage so therapy can be initiated early, before extensive damage is done.
Type II collagen constitutes the bulk of the fibrillar backbone of the cartilage matrix, just as type I collagen forms the fibrillar organization of the extracellular matrix of most other tissues such as skin, bone, ligaments and tendons. These collagens are composed of a tightly wound triple helix, which can only be cleaved by metalloproteinase collagenases to produce 3/4 and 1/4 length .alpha.-chain fragments that are identifiable by polyacrylamide gel electrophoresis.
The destruction of articular cartilage during arthritic disease is due, in part, to the degradation of the extracellular matrix, which is composed primarily of fibrillar type II collagen and aggregating proteoglycans. In articular cartilage, type II collagen fibrils are responsible for the tensile strength whereas the proteoglycans provide the compressive stiffness necessary for normal articulation and function. The precise mechanisms by which these connective tissue components are degraded are not fully understood. In mammals, an important mechanism involves the collagenases which are a group of enzymes capable of site-specific cleavage of helical (native) collagen.